Survival of children with endemic Burkitt lymphoma in a prospective clinical care project in Uganda

Abstract

Purpose “Endemic” Burkitt lymphoma (BL) is a common childhood cancer in Africa. Social and treatment factors may contribute to poor survival. With the aim of improving BL outcomes in Uganda, we undertook a comprehensive project (BL Project) that provided diagnostic support, access to standard chemotherapy, nutritional evaluations, and case management. We evaluated survival of children with BL in the context of the project. Patients and methods Patients followed by the BL Project who consented to research were enrolled in this study. Children with a pathology diagnosis consistent with BL were eligible. Data were collected prospectively. First‐line chemotherapy generally consisted of six cycles of cyclophosphamide, vincristine, low‐dose methotrexate (COM). We used Kaplan–Meier and Cox regression analyses to evaluate factors associated with overall survival (OS). Results Between July 2012 and June 2017, 341 patients with suspected BL presented to the BL Project. One hundred eighty patients with a pathology‐based diagnosis were included in this study. The median age was seven years (interquartile range, 5–9), 74% lived ≥100 km from the Uganda Cancer Institute, 61% had late‐stage disease, 84% had ECOG performance status < 3, 63% reported B‐symptoms, and 22% showed neurologic symptoms. Fewer than 10% abandoned therapy. The four‐year OS rate was 44% (95% CI, 36%–53%). In a multivariate model, ECOG status was significantly associated with mortality. Conclusion The BL Project reduced effects of lacking supportive care and oncology resources, and allowed patients from Uganda to receive curative intent therapy with minimal loss to follow‐up. Nonetheless, OS remains unacceptably low. Improved therapeutic approaches to endemic BL are urgently needed in Africa.

Sustainable care for children with cancer: a Lancet Oncology Commission

“…100 Optimization of care has shown to be possible even in the poorest countries as exemplified by the design of effective regimens for Burkitt lymphoma, one of the most common cancers in Africa, adapted to the socioeconomic conditions, the available supportive care, and the patients' co-morbidities. 101 For example, in Malawi, a simple protocol costing less than $50 per 28-day cycle resulted in 1-year survival of 48%. 102 And in Uganda, the cost per Disability Adjusted Life Year (DALY) averted in a cohort of children with Burkitt lymphoma was $97.…”

Five decades of low intensity and low survival: adapting intensified regimens to cure pediatric Burkitt lymphoma in Africa

“…17,20,51,52 A recent clinical quality improvement project at the Uganda Cancer Institute is emblematic of the lack of progress in improving outcomes: over a 5-year period (2012-2017), 180 children with pathology-confirmed diagnoses of BL were treated with COM, with resources dedicated to ensuring accurate diagnosis, chemotherapy availability, and treatment compliance. 44 Despite mitigating limitations of access to care, the 4-year OS was 44%, 44 similar to results from clinical trials at the same center from the 1970s. 53 Although the International Network for Cancer Treatment and Research had earlier reported event-free survival (EFS) and OS of 54% and 67%, respectively, at 1 year using a similar regimen with a slightly higher dose of MTX (75 mg/m 2 compared with doses of 15-45 mg/m 2 used in other COM trials), that study built in a salvage regimen of ifosfamide, etoposide, and cytarabine for patients who failed COM.…”

“…25,27,[36][37][38][39][40][41] Survival rates have plateaued over the past 40 years, and efforts to improve have stalled since then. Contemporary efforts to improve outcomes within the cyclophosphamidebased paradigm have included the addition of various low doses of MTX, [42][43][44] vincristine, 45 doxorubicin, and prednisone. 17,20,46,47 The collective experience has demonstrated cohort survival rates ranging from 30% to 50%, with mortality primarily attributed to tumor progression or recurrence (Table 1).…”

Pediatric lymphoma patients in Malawi present with poor health-related quality of life at diagnosis, and improve throughout treatment and follow-up across all Pediatric PROMIS-25 domains.

“…43 One-year overall survival was 47% (95% CI [37-59%]), which is consistent with historical and published survival rates for Burkitt lymphoma across SSA, and is significantly worse than reported survival rates of >90% in HIC. 2,22,[43][44][45][46][47] Given the high mortality and the challenges associated with cancer treatment in resource-poor health systems, appropriate risk stratification of patients is critical in SSA, where administering aggressive treatment to optimize survival must be weighed against toxicity risks for vulnerable children. Poor LPS has consistently been identified as a risk factor for mortality in research from both LMICs and HICs.…”

“…Poor LPS has consistently been identified as a risk factor for mortality in research from both LMICs and HICs. 2,22,45,46,48 Further, emerging data from HICs suggest PROs offer superior assessment of performance status when compared to traditional physician-reported measures. 49 We observed significantly increased mortality risk and worse survival in our cohort among patients with physician-reported LPS [?]…”